Machine learning-assisted label-free colorectal cancer diagnosis using plasmonic needle-endoscopy system.

Early and accurate detection of colorectal cancer (CRC) is critical for improving patient outcomes. Existing diagnostic techniques are often invasive and carry risks of complications. Herein, we introduce a plasmonic gold nanopolyhedron (AuNH)-coated needle-based surface-enhanced Raman scattering (SERS) sensor, integrated with endoscopy, for direct mucus sampling and label-free detection of CRC. The thin and flexible stainless-steel needle is coated with polymerized dopamine, which serves as an adhesive layer and simultaneously initiates the nucleation of gold nanoparticle (AuNP) seeds on the needle surface. The AuNP seeds are further grown through a surface-directed reduction using Au ions-hydroxylamine hydrochloride solution, resulting in the formation of dense AuNHs. The formation mechanism of AuNHs and the layered structure of the plasmonic needle-based SERS (PNS) sensor are thoroughly analyzed. Furthermore, a strong field enhancement of the PNS sensor is observed, amplified around the edges of the polyhedral shapes and at nanogap sites between AuNHs. The feasibility of the PNS sensor combined with endoscopy system is further investigated using mouse models for direct colonic mucus sampling and verifying noninvasive label-free classification of CRC from normal controls. A logistic regression-based machine learning method is employed and successfully differentiates CRC and normal mice, achieving 100% sensitivity, 93.33% specificity, and 96.67% accuracy. Moreover, Raman profiling of metabolites and their correlations with Raman signals of mucus samples are analyzed using the Pearson correlation coefficient, offering insights for identifying potential cancer biomarkers. The developed PNS-assisted endoscopy technology is expected to advance the early screening and diagnosis approach of CRC in the future.

Histone Lactylation Drives CD8 T Cell Metabolism and Function.

The activation and functional differentiation of CD8 T cells are linked to metabolic pathways that result in the production of lactate. Lactylation is a lactate-derived histone post-translational modification (hPTM); however, the relevance of histone lactylation in the context of CD8 T cell activation and function is not known. Here, we show the enrichment of H3K18-lactylation (H3K18la) and H3K9-lactylation (H3K9la) in human and murine CD8 T cells which act as transcription initiators of key genes regulating CD8 T cell phenotype and function. Further, we note distinct impacts of H3K18la and H3K9la on CD8 T cell subsets linked to their specific metabolic profiles. Importantly, we demonstrate that modulation of H3K18la and H3K9la by targeting metabolic and epigenetic pathways regulates CD8 T cell effector function including anti-tumor immunity in preclinical models. Overall, our study uncovers the unique contributions of H3K18la and H3K9la in modulating CD8 T cell phenotype and function intricately associated with metabolic state.

Tumor Pre-Targeting System Using Streptavidin-Expressing Bacteria.

PURPOSE: A major obstacle to targeted cancer therapy is identifying suitable targets that are specifically and abundantly expressed by solid tumors. Certain bacterial strains selectively colonize solid tumors and can deliver genetically encoded cargo molecules to the tumor cells. Here, we engineered bacteria to express monomeric streptavidin (mSA) in tumors, and developed a novel tumor pre-targeting system by visualizing the presence of tumor-associated mSA using a biotinylated imaging probe. PROCEDURES: We constructed a plasmid expressing mSA fused to maltose-binding protein and optimized the ribosome binding site sequence to increase solubility and expression levels. E. coli MG1655 was transformed with the recombinant plasmid, expression of which is driven by the pBAD promotor. Expression of mSA was induced by L-arabinose 4 days after injection of bacteria into mice bearing CT26 mouse colon carcinoma cells. Selective accumulation of mSA in tumor tissues was visualized by optical imaging after administration of a biotinylated fluorescent dye. Counting of viable bacterial cells was also performed. RESULTS: Compared with a conventional system, the novel expression system resulted in significantly higher expression of mSA and sustained binding to biotin. Imaging signals in tumor tissues were significantly stronger in the mSA-expressing group than in non-expressing group (P = 0.0005). Furthermore, the fluorescent signal in tumor tissues became detectable again after multiple inductions with L-arabinose. The bacterial counts in tumor tissues showed no significant differences between conditions with and without L-arabinose (P = 0.45). Western blot analysis of tumor tissues confirmed expression and binding of mSA to biotin. CONCLUSIONS: We successfully engineered tumor-targeting bacteria carrying a recombinant plasmid expressing mSA, which was targeted to, and expressed in, tumor tissues. These data demonstrate the potential of this novel tumor pre-targeting system when combined with biotinylated imaging probes or therapeutic agents.

Long-term outcomes after haploidentical stem cell transplantation for hematologic malignancies.

ABSTRACT: The introduction of posttransplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis lead to significant improvements in haploidentical stem cell transplantation (haplo-SCT) outcomes over the past decade. We retrospectively assessed long-term outcomes of patients who had their first haplo-SCT between February 2009 and March 2019. Long-term survivors were defined as patients who were alive and disease-free at 2 years after transplant. Three hundred thirty-five patients with a median age of 48 years (range, 18-72) were identified. Of these, 142 patients were disease-free and alive at 2 years after transplant. The 4-year progression-free survival (PFS) and overall survival (OS) for all study patients were 42% and 47%, respectively. With a median follow-up of 52 months for the long-term survivor group, the 4-year PFS and OS were 94% and 96%, respectively. The 4-year cumulative incidence of relapse and non-relapse mortality (NRM) were 2.9% and 3.3%, respectively. Age ≥55 years was the only predictive factor in multivariate analysis for inferior PFS (hazard ratio [HR], 3.41; 95% confidence interval [CI], 1.21-9.60; P = .020) and OS (HR, 3.31; 95% CI, 1.08-10.18; P = .037). Thirteen patients (9%) died in the long-term survivor group, only 2 of whom died of relapsed disease. Secondary primary malignancy was the most frequent cause of NRM (n = 4), followed by infection (n = 2). For haplo-SCT with PTCy-based GVHD prophylaxis, our findings suggest an excellent long-term survival for patients who were disease-free and alive at 2 years after transplant. Late relapses were rare, and age was the only predictive factor for long-term outcomes.

Endoscopic Hyperspectral Imaging System to Discriminate Tissue Characteristics in Tissue Phantom and Orthotopic Mouse Pancreatic Tumor Model.

In this study, we developed an endoscopic hyperspectral imaging (eHSI) system and evaluated its performance in analyzing tissues within tissue phantoms and orthotopic mouse pancreatic tumor models. Our custom-built eHSI system incorporated a liquid crystal tunable filter. To assess its tissue discrimination capabilities, we acquired images of tissue phantoms, distinguishing between fat and muscle regions. The system underwent supervised training using labeled samples, and this classification model was then applied to other tissue phantom images for evaluation. In the tissue phantom experiment, the eHSI effectively differentiated muscle from fat and background tissues. The precision scores regarding fat tissue classification were 98.3% for the support vector machine, 97.7% for the neural network, and 96.0% with a light gradient-boosting machine algorithm, respectively. Furthermore, we applied the eHSI system to identify tumors within an orthotopic mouse pancreatic tumor model. The F-score of each pancreatic tumor-bearing model reached 73.1% for the KPC tumor model and 63.1% for the Pan02 tumor models. The refined imaging conditions and optimization of the fine-tuning of classification algorithms enhance the versatility and diagnostic efficacy of eHSI in biomedical applications.

Safety and long-term survival results of the addition of inotuzumab ozogamicin to the conditioning regimen of allogeneic stem cell transplantation: A single-center phase 1,2 trial.

Here we report on the first prospective study evaluating the safety and long-term survival when an escalating dose of inotuzumab ozogamicin (INO) (0.6, 1.2, or 1.8 mg/m2 on day 13) was added to one alkylator-containing conditioning regimen in patients with relapsed CD22 (+) lymphoid malignancies who were candidates for hematopoietic stem cell transplantation (HSCT). Twenty-six patients were enrolled. Six (23%) of these patients entered the phase 1 study: four were treated at an INO dose of 0.6 mg/m2 and two at dose of 1.2 mg/m2. None of these patients experienced dose-limiting toxicities. The remaining 20 (77%) patients entered the phase 2 part of the study at the maximum dose of 1.8 mg/m2. One patient developed VOD; this patient had received nivolumab immediately before HSCT while simultaneously experiencing hyperacute graft-vs-host disease (GVHD). Treatment-related mortality (TRM) at 5 years was 12%. With a median follow-up of 48.7 months, the 5-year overall survival (OS) and progression-free survival (PFS) rates were 84% and 80%, respectively. Compared with a historical cohort who received same conditioning for HSCT but without INO (n = 56), the INO group showed no significant differences in incidence of liver toxicity, engraftment time, TRM, or risk of acute GVHD. Patients with lymphoma who received INO had a trend for a better 5-year OS (93% versus 68%) and PFS (93% versus 58%) than those in the control group. In conclusion, our results showed that INO is safe with no increased risk of VOD when combined with one alkylator-containing regimen of HSCT.

Exploring the Effect of Deep-Sea Water on the Therapeutic Potential of the Anti-Inflammatory Response in an Indomethacin-Induced Gastric Ulcer Rat Model.

Gastric ulcers are often exacerbated by factors such as nonsteroidal anti-inflammatory drugs (NSAIDs) and inflammation, and they have a substantial impact on a significant portion of the population. Notably, indomethacin is recognized as a prominent contributor to ulcers. This study investigated this potential method, with normalization to the anti-inflammatory and antiulcer properties of deep-sea water (DSW)-derived mineral water, using an indomethacin-induced gastric ulcer model in rats. The study involved four groups (n = 6 rats/group): normal control group (CON), indomethacin-only group (IND), indomethacin with trace mineral water group (TM), and indomethacin with high magnesium low sodium water group (HMLS). For three weeks, the CON and IND groups consumed tap water, while the TM and HMLS groups had access to mineral water. Gastric ulcers were induced on the final day using indomethacin, for all groups except the CON group. The results demonstrated that HMLS intake significantly improved gastric mucosal damage, preserved mucin stability, and increased gastric thickness, indicating its potential to prevent and alleviate indomethacin-induced gastric ulcers. Furthermore, HMLS consumption led to the upregulation of key genes associated with inflammation and a reduction in inflammatory cytokines. These findings suggest that DSW-derived mineral water, and particularly its high Mg2+ content, may offer promising health benefits including anti-inflammatory and anti-ulcer properties.

Association Between Psychiatric Medications and Urinary Incontinence / 정신신체의학

Urinary incontinence (UI), affecting 3%-11% of males and 25%-45% of females globally, is expected to rise with an aging population. It significantly impacts mental health, causing depression, stress, and reduced quality of life. UI can exacerbate psychiatric conditions, affecting treatment compliance and effectiveness. Itis categorized into transient and chronic types. Transient UI, often reversible, is caused by factors summarized in the acronym DIAPPERS: Delirium, Infection, Atrophic urethritis/vaginitis, Psychological disorders, Pharmaceuticals, Excess urine output, Restricted mobility, Stool impaction. Chronic UI includes stress, urge, mixed, overflow, functional, and persistent incontinence. Drug-induced UI, a transient form, is frequently seen in psychiatric treatment. Antipsychotics, antidepressants, and other psychiatric medications can cause UI through various mechanisms like affecting bladder muscle tone, altering nerve reflexes, and inducing other conditions like diabetes or epilepsy. Specific drugs like lithium and valproic acid have also been linked to UI, though mechanisms are not al-ways clear. Managing UI in psychiatric patients requires careful monitoring of urinary symptoms and judiciousmedication management. If a drug is identified as the cause, options include discontinuing, reducing, or adjusting the dosage. In cases where medication continuation is necessary, additional treatments like desmopressin, oxybutynin, trihexyphenidyl, or amitriptyline may be considered.

Identification of Free-Living Amoebas in Tap Water of Buildings with Storage Tanks in Korea

Free-living amoebas (FLAs) can cause severe disease in humans and animals when they become infected. However, there are no accurate survey reports on the prevalence of FLAs in Korea. In this study, we collected 163 tap water samples from buildings, apartments, and restrooms of highway service areas in 7 Korean provinces with high population density. All these buildings and facilities have water storage tanks in common. The survey was separated into categories of buildings, apartments, and highway service areas. Five hundred milliliters of tap water from each building was collected and filtered with 0.2 µm pore filter paper. The filters were incubated in agar plates with heated E. coli at 25°C. After axenization, genomic DNA was collected from each FLA, and species classification was performed using partial 18S-rDNA PCR-sequencing analysis. We found that 12.9% of tap water from buildings with storage tanks in Korea was contaminated with FLAs. The highway service areas had the highest contamination rate at 33.3%. All of the FLAs, except one, were genetically similar to Vermamoeba vermiformis (Hartmannella vermiformis). The remaining FLA (KFA21) was very similar to Acanthamoeba lugdunensis (KA/E26). Although cases of human infection by V. vermiformis are very rare, we must pay attention to the fact that one-third of tap water supplies in highway service areas have been contaminated.

Grit, Academic Resilience, and Psychological Well-being in Nursing Students / 한국간호교육학회지

PURPOSE: This study was conducted to investigate the relationship among grit, academic resilience, and psychological well-being among nursing students. METHODS: The participants were 271 nursing students, enrolled in C university. Data were collected from September 5 to 30, 2016 and analyzed using descriptive analysis, t-test, ANOVA, Pearson correlation coefficients, and stepwise multiple regression with the SPSS/WIN 21.0 program. RESULTS: The mean scores for academic resilience were above average. The mean score for grit and psychological well-being presented an appropriate level. Psychological well-being in nursing students was significantly correlated with academic resilience (r=.65, p<.001) and grit (r=.52, p<.001). The significant predictors of psychological well-being for nursing students were academic resilience (β=.47, p<.001), grit (β=.26, p<.001), and major satisfaction (β=.20, p<.001) which explained 53.1% of the variance in psychological well-being. CONCLUSION: The results indicate that it is necessary to develop grit and academic resilience enhancement programs to improve the psychological well-being of nursing students.

A Case of Leg Monoparesis with Sensory Deficit Due to Cerebral Infarction / 대한뇌졸중학회지

A male patient aged 54 came to the neurology department complaining of weakness and tingling sensation in the left lower extremity during squatting exercises for the previous four days. A neurological examination revealed left proximal leg weakness and hypesthesia on the medial side of the left lower leg. In eight hours after onset, he took brain and lumbar MRIs at a local clinic and the results were normal. In order to identify possible causes, we performed a follow-up lumbar MRI, femoral angiography, electromyography, and nerve conduction study but failed to obtain any abnormal findings. Finally, a recent infarction of right corona radiata was observed by a follow-up brain MRI which was taken 16 days after onset of the symptom. Leg monoparesis caused by cerebral infarction is known to be rare and in particular combines motor and sensory deficits limited to one extremity.

Cerebral Toxocariasis Presented With Seizure and Memory Disturbance

Toxocariasis has a broad clinical spectrum, from asymptomatic to systemic illness. However, cerebral toxocariasis has rarely been reported. We experienced a patient who presented with seizure and memory disturbance after treatment for visceral larva migrans of toxocariasis. Laboratory findings included eosinophilia, cerebrospinal fluid (CSF) pleocytosis, and positive results for toxocariasis in the serum and CSF. The patient showed marked improvement after combined albendazole and steroid treatment. This case indicates that cerebral toxocariasis is an unusual cause of cognitive dysfunction and seizure.

Pure Retrograde Amnesia: Is This Real Organic or Psychogenic?

Cases showing memory disturbances with isolated retrograde memory without any definitive brain lesions are classified as dissociative amnesia. Improvements in imaging techniques have allowed the organic causes of this disease to be identified in several recent cases. Several studies have diagnosed cases of memory disorders as pure retrograde amnesia (PRA). The patient reported here had no psychiatric disorder and had normal MRI results, but showed hypometabolism in PET that met the criteria for PRA.

A Cerebellar Infarction Presented with a Clinical Seizure / 대한간질학회지

Classically, only lesions in the cerebral cortex have been thought to cause the epilepsy. Although the cerebellar infarction is presented with ataxia, dysmetria and dizziness, we experienced a patient of cerebellar infarction developed immediately after or simultaneously with a clinical seizure. A brain magnetic resonance imaging (MRI) showed acute cerebellar infarction on the bilateral cerebellar hemisphere.